Acomb Rabbit Rescue is now closed and no longer taking in rabbits.
Thank you to everyone who has supported us for the last six years.
Thank you to everyone who helped to make our stall at the Fulford Show today such a great success. We raised £108! We've done 25 of these stalls now & that's the most we've ever made! It all goes towards neutering & vaccinating the buns so they can find great new homes.
We'll be at the Fulford Show tomorrow from 1pm - 5pm. Paws crossed for nice weather!
Our stall at the West Bank Park Summer Fair today was a great success. The weather was lovely, and we raised £63.20! Our next stall will be at the Fulford Show on Monday 28th August.
Our first stall of the year will be at the West Bank Park Summer Fair on Sunday 9th July from 1-4pm. Paws crossed for good weather!
VHD2 is a variant of the deadly VHD disease. We were very relieved when our vets began to stock the Filavac vaccine which protects rabbits against this devastating disease, however vaccinating all of the rescue rabbits has sadly eaten up all of our funds. We don't want to raise our £50 adoption fee as this may put too many potential adopters off and our waiting list of rabbits in need is huge. We hope that one day there will be a single vaccine available that protects against myxomatosis, VHD1 and VHD2, lowering our costs, but until then we need your help. Please help by donating whatever you can, every little helps. Our Paypal address is acombrabbitrescue@hotmail.co.uk (please select the 'friends and family' option so we don't have to pay a fee).
Thank you to everyone who donated items for the stall or came down to the Fulford Show. We raised £74.05! That's our last stall for this year, but please get in touch if you know of any events we could attend to raise funds.
Great weather for the Dunnington Fayre today, and we raised £24.50. Our next stall will be at the Fulford Show on Monday 29th August. If you have any items to donate, please get in touch.
Yesterday's stall at the West Bank Park Summer Fair was a great success. We raised £91.94! Our next stall will be at the Rowntree Park Birthday Party on Sunday 17th July. We're now running low on our best selling items, like gift sets and children's toys. If you have any to donate, please get in touch.
Hop on down to Lush this Easter weekend and grab yourself a fabulous Charity Pot, with all proceeds except VAT going to us! They'll be open Friday, Saturday and Monday.
UPDATE: A huge thank you to the team at Lush and everyone who bought a Charity Pot over the Easter weekend. You've raised an amazing £432.50!
If you're in York, hop on down to Waitrose this month as they're supporting us through their Community Matters Scheme. Just pop a green token in our box and help us to raise funds!
UPDATE: Thank you to everyone who supported us, you've helped to raise £235!
It was a cold and wet day at the Fulford Show, but we still managed to raise a respectable £32.03.
That's the last stall we have booked for this year, but if you know of a local event that we could have a stall at to raise money, please get in touch.
It was a great day at the Acomb Green Summer Fair, and we raised a record breaking £101.25! Our next stall will be at the Fulford Show on Monday 31st August.
Thank you to everyone who has signed up to Easy Fundraising to help us raise funds while you shop online. This quarter you've helped to raise an amazing £48.37!
The sun was shining at the Dunnington Fayre today, and we made £27.90. Our next stall will be at the Acomb Green Summer Fair on Saturday 29th August.
It was a very windy day at the Rowntree Park Birthday Party. The gazebo looked drunk and one of the poles snapped, but thanks to some kind volunteers and members of the public it stayed up until the end, and we made £30!
We had a great day at the West Bank Park Summer Fair, and raised £55! There was a bit of rain and wind, but also a bit of sunshine. Our next stall will be at the Rowntree Park Birthday Party on Sunday 12th July. If you have any items to donate, please get in touch.
It was a bit chilly and ridiculously windy at the Acomb Primary School Fair, but still a good day. We raised £46.45! Our next stall will be at the West Bank Park Summer Fair on Sunday 28th June from 1-4pm, but we're running low on stock now. If you have any items to donate, particularly toys and gift sets, please get in touch.
The summer issue of Rabbiting On is now available and we're very proud to be in it! Acomb Rabbit Rescue has been chosen as one of the four rescues for this year's 'Sponsor a Rescue' scheme. To get your copy please join the Rabbit Welfare Association: http://www.rabbitwelfare.co.uk/ The RWAF are the best source of up to date advice and information on rabbits.
We had a great day today at our first stall of the year, at the Copmanthorpe Street Fair. The sun was shining and we raised £70.70!
Our next stall will be at the West Bank Park Summer Fair on Sunday 28th June. If you have any items to donate for the stall (books, toys, bric a brac etc.) we can collect from the York area.
Thank you to everyone who has signed up to Easy Fundraising to help us raise funds while you shop online. This quarter you've helped to raise a whopping £35.27!
Adorable hand crafted bunny brooches and keyrings for sale!
Ideal stocking fillers for bunny lovers!
Brooches are £2 each + 73p postage. Available in pink, green and blue. Made from felt with fluffy pom pom tails.
Keyrings are £2.50 each + 73p postage. Only one purple one available now, but we may have more soon.
Button brooches are £2 each + 73p postage. Available in yellow, orange, blue and light blue.
We had a stall at the Battle Flatts Charity Fun Day today and raised £10.50!
We have no more stalls booked this year, so if you know of any events we could attend, please get in touch.
Thank you to everyone who donated much needed stock for the fair.
Our next stall will be at the Fulford Show on bank holiday Monday 25th August from 1-5pm.
It was a long, hot day at the Dunnington Fayre yesterday, but we raised £26.90. Our next stalls will be at the Acomb Green Summer Fair on Saturday 23rd August from 1pm-4pm and the Fulford Show on Monday 25th August from 1pm-5pm. If you know of any other summer events that we could book a stall at, please let us know.
Great to meet so many people at the Rowntree Park Birthday Party today. Shame about the rain, but at least it didn't last all day! Unfortunately, we only raised £13.20. Our next stall is on Saturday 26th July at the Dunnington Fayre, from 11am-4pm.
Misty is a blind 7 year old rex who lost her partner to cancer in April. She has arthritis which causes sore hocks, and has recently become worse. She's had xrays which showed the extent of the damage to her joints, and she's now being referred to a specialist in acupuncture and pain management. Misty still has a good quality of life, and we hope we can make her more comfortable with the new treatment plan. But it's expensive. So if you can donate anything at all, no matter how small, to help towards Misty's care please do.
Misty has now found a wonderful new home, where she can continue her acupuncture treatment, and she has a new husbun, Reggie.
We had a great time at the West Bank Park Summer Fair. The forecast was for rain, but luckily it stayed dry and sunny. We raised £70.50 and spoke to a lot of people interested in adopting rabbits. The next fair we'll be at is the Rowntree Park Birthday party on Sunday 20th July.
We had a great day at the Copmanthorpe Street Fair, and raised £67.20! Thank you to everyone who donated items for the stall. The next stall will be at the West Bank Park Summer Fair on Sunday 29th June from 1-4pm.
From 1st May, Acomb Rabbit Rescue will be one of the three local charities chosen for Waitrose Community Matters. So when you shop in Waitrose in York you'll get a token to put in one of three boxes. At the end of the month we get a share of £1000 based on how many tokens are put in our box. Please get shopping at Waitrose in York and put a token in our box to help us to win some much needed funds!
We've booked another two stalls at local events this year. We'll be at the West Bank Park Summer Fair on Sunday 29th June from 1-4pm and the Rowntree Park Birthday Party on Sunday 20th July.
Thank you to everyone who has signed up to Easy Fundraising to help us raise funds while you shop online. This quarter you've helped to raise a whopping £83.27!
We've just booked our first stall of the year, on bank holiday Monday 5th May at the Copmanthorpe Street Fair. Please get in touch if you have any unwanted Christmas presents, toys or books to donate. Thank you.
If you're thinking of donating something to the ARR buns for Christmas but you're not sure what they need, these are the things we use most often: Hay (we buy bales so bags of different types of hay or with tasty bits included are always appreciated by the buns), Megazorb (or other paper based litter), Graze-On (also known as Readigrass and Just Grass), Panacur rabbit worming paste, forage (either fresh or dried), treats (like fenugreek crunchies) and toys.
We are in need of large litter trays for the bigger buns and pairs, under-bed storage boxes are ideal. We also have an Amazon Wishlist. If you're using Amazon or any online retailer this Christmas, please join Easy Fundraising to help us raise money every time you shop!
Thank you to everyone who supports us by using Easy Fundraising, this quarter you've helped raise £31.16!
We'll be holding a stall at the Christmas Fair at Carr Junior School on Ostman Road, Acomb, on Saturday 30th November from 1pm - 3pm. Come along and say hi!
UPDATE: Thank you to everyone who donated items for the Christmas Fair, we raised £39.60!
Thank you to everyone who uses Easy Fundraising to support the rescue. This quarter you've helped to raise £12.53! If you're not already signed up then take a look. You can raise money while you shop and it won't cost you a penny!
We have another couple of stalls booked for the summer. We'll be at the Hull Road Summer Fair on Saturday 3rd August from 1pm - 3.30pm, and the Acomb Green Summer Fair on Saturday 24th August from 1pm - 4pm. If you have any items you would like to donate for the stalls, like toys, books and bric a brac, please get in touch.
UPDATE: We raised £50.75 at the Hull Road Summer Fair! It was a great day, despite the wind that nearly stole the gazebo! Thank you to everyone who donated items for us to sell. There's still time to donate for the Acomb Green Summer Fair on the 24th August. If anyone has a folding/pasting table they don't need any more it would be greatly appreciated - ours is on its last legs!
UPDATE: Sadly the Acomb Green Summer Fair was cancelled due to the weather, but we had a great day at the Fulford Show two days later. A beautiful day and we raised an amazing £78! That's the last of the summer fairs for this year, but if you know of any events where we could hold a stall over the next few months please let us know.
We will be having another stall at the Dunnington Fayre on Saturday 20th July, from 11am - 4pm. There'll be lots of rabbit information and lots for sale, like toys, books, clothes and bric a brac. Come along and say hi!
UPDATE: Thank you to everyone who bought, donated or came to say hi to us at the Dunnington Fayre yesterday. We had a good day (despite the clouds and the wind!) and raised £26.
A big thank you again to the Pledge a Pound team who have organised a special summer fundraiser to provide ice pods for rescues. The ice pods we've received will be greatly appreciated by the buns.
We will be having a stall at the Copmanthorpe Carnival, so if you're going come over and say hi! There'll be lots of information about rabbits and lots for sale, including toys, books, jewellery and bric a brac.
UPDATE: Thank you to everyone who bought, donated and came over to say hello. We raised £25, and hopefully raised awareness of the rescue and of rabbit welfare in general. It was a great day!
Thank you to everyone who supports and donates to Pledge A Pound. The £70 donation we have received will go towards the vet bills for Thumper, who arrived with a broken front tooth that needed removing and blocked tear ducts that needed flushing, and Dylan who arrived with an awful ear mite infestation and needed his ears cleaning and a course of mite treatment.
If anyone can help, we're always in need of lino for the pens, large litter trays/storage boxes and large carriers. We also use a lot of old newspaper, hay and megazorb. With so many buns, toys, treats and forage (either fresh or dried) are always appreciated.
Pets At Home have donated £200 to the rescue, which will go towards the cost of treatment for some of the poorly buns here at the moment.
After another successful stall today the amount raised is £18.40. Thank you to everyone who came along and said hi or donated. And thank you to a special Facebook follower who has doubled the amount raised, making a grand total of £36.80!
The bunshed insulation project is now complete! The rescue buns will now be toasty warm next winter.
Handmade Easter bunny biscuits! Back by popular demand are carrot & coriander flavour and apple & parsley flavour. Made from the finest SS pellets, oats and readigrass, with fresh carrot & coriander or apple & parsley. Approximately 100g of nommy goodness in each bag. £6 for one bag (price increase due to having to change from Royal Mail to Hermes for delivery ), £10 for two. Prices include postage. The number of biscuits varies between 14-20 per bag, as they're different sizes. Orders will be posted the next day.
Today is our first anniversary! In our first year we have rehomed 15 rabbits. Thank you to everyone who has supported us, donated and adopted from us.
Valentine's bunny biscuits are now available! Choose from either the new carrot & coriander flavour, or back by popular demand, apple & parsley flavour.
Made from the finest SS pellets, oats and readigrass, with fresh carrot & coriander or apple & parsley. Approximately 100g of nommy goodness in each bag. £5.50 for one bag, £10 for two. Prices include postage. The number of biscuits varies between 14-20 per bag, as they're different sizes. Orders will be posted the next day.
Christmas bunny biscuits for sale! Choose from either apple & parsley or banana flavour. Made with SS pellets, oats, readigrass and fresh veg and herbs, your bun will love these tasty treats! Approximately 100g of nommy goodness in each bag. £5.50 for one bag, £10 for two. Prices include postage. The number of biscuits varies between 14-20 per bag, as they're different sizes. Please send an email with your address and how many bags you'd like. Orders will be posted the next day.
We've just signed up to Easy Fundraising. If you register and choose Acomb Rabbit Rescue, we'll get a donation every time you shop at certain online stores, like Amazon, and it won't cost you a penny!
After a successful stall today we raised £28! Thank you to everyone who came along and said hi or donated.
We now have an Amazon wishlist with a selection of essentials, toys and treats. If anyone would like to buy the buns a present, find us with our email address.
We now have a Paypal account for donations.


text:
Details about Africa: War and Conflict in the Twentieth Century (Seminar Studies) by Stapleton
Africa: War and Conflict in the Twentieth Century (Seminar Studies) by Stapleton
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The pursuit of a cure for HIV infection has become a central plank of the overall research portfolio, and this has been officially underpinned by the revised HIV/AIDS priorities announced by the U.S. National Institutes of Health (NIH) in 2015.1,2 The NIH has cited the goal of developing a cure for HIV/AIDS as one of five high-priority areas for HIV/AIDS research, and only grant applications that address these priorities will be considered for funding from 2016 onwards.
The number of clinical trials and observational studies related to the effort to cure HIV has expanded further over the past year (see table 1). However, this work remains largely exploratory; among the main lines of research being pursued, investigators are probing a variety of possible means to try and diminish the reservoir of HIV that persists in the body despite antiretroviral therapy (ART). Strategies for inducing containment of the virus when ART is interrupted are also being explored, including gene therapies and immune-based therapies (particularly therapeutic vaccines). These are early-stage tests, and it is important to appreciate that there is no prospect of study participants being cured; the hope is that the information gleaned will guide scientists toward curative approaches.
Brown received stem cell transplants from a CCR5-Δ32 homozygote as part of a grueling series of treatments for acute myelogenous leukemia nearly a decade ago, and no trace of replication-competent HIV has been detected in his body since that time, despite the discontinuation of ART.6 At least six individuals have since been reported who underwent similar procedures, but all of them died as a result of either the underlying cancers or complications from the transplantation procedure.7 One new case was described in a poster at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI), and the preliminary signs appear encouraging: the cancer is in remission and HIV cannot be detected using multiple techniques.8 However, ART had not yet been interrupted at the time of the presentation, so it is too early to know whether this may represent a second example of an HIV cure.
Despite the fallowness of this field, there does remain a need for therapies capable of addressing the elevated risk of morbidity and mortality faced by individuals who experience a poor immunologic response to ART.10 The single most important risk factor for becoming an immunologic non-responder (INR) is late initiation of ART, and the most recently available surveillance data from the U.S. Centers for Disease Control and Prevention indicate that this remains a problem despite efforts to promote early diagnosis: in 2013, 41,661 individuals were newly diagnosed with HIV infection, and 23.6% had progressed to AIDS at the time of diagnosis.11 TAG is currently collaborating with other activists to explore whether candidate treatments for INRs might be considered as orphan drugs, a U.S. Food and Drug Administration (FDA) designation intended to spur the development of treatments for disorders that are relatively rare.
In the new trial, a series of six immunizations with Vacc-4x and GM-CSF adjuvant were administered, followed by three infusions of romidepsin, to 17 participants on ART. Levels of total HIV DNA, one possible surrogate measure of the reservoir, showed a statistically significant decline of 39.7%. An alternate assay measuring HIV DNA that is integrated into the genome of CD4 T cells also documented a slight reduction, but this did not reach statistical significance. Replication-competent HIV was detectable in six participants at baseline using a viral outgrowth assay, and levels fell significantly after the interventions by around 38%.
In the final stage of the study, 16 participants underwent an ART interruption. Despite the evidence of a small decline in HIV reservoir size, there was no delay in viral load rebound in any participant. In his CROI presentation, Søgaard concluded that the data offer some support for the idea of combining LRAs with therapeutic vaccines, but improvements are needed to enhance the magnitude of the effect.
The multicenter RIVER trial in the UK, investigating vorinostat together with two viral-vector-based HIV vaccines derived from chimpanzee adenovirus and a modified Vaccinia Ankara strain (MVA).
A study at the IrsiCaixa institute in Spain looking at romidepsin and an MVA-based HIV vaccine.
A combination of vorinostat with AGS-004, a dendritic-cell-based vaccine that is personalized to present HIV antigens obtained by sampling viral sequences from each intended recipient, which is being tested at the University of North Carolina.
Other types of combinations are also being explored, with several new protocols being launched or imminent since last year. Among them is a trial of the HDAC inhibitor panobinostat and the cytokine pegylated interferon-α2a that is being conducted at Massachusetts General Hospital by Dan Kuritzkes, Mathias Lichterfeld, and Rajesh Gandhi. The rationale derives from a previously published study of panobinostat that reported that a small subset of participants appeared to experience a diminution of the HIV reservoir that correlated with a delay in viral rebound after ART interruption.14 An analysis led by Mathias Lichterfeld found that this response was partly linked to interferon-stimulated genes,15 suggesting that interferon may be able to potentiate the effects of panobinostat on the HIV reservoir.
Earlier this year, Joe Eron from the University of North Carolina debuted data from the first trial of an antibody targeting the PD-1 pathway in people with HIV. The antibody in question is manufactured by Bristol-Myers Squibb and does not bind to PD-1, but rather to a ligand that it interacts with, PD-L1. The original intent was to study single infusions of various, escalating doses in people on suppressive ART; however, only the lowest dose (0.3 mg/kg) was administered due to an unexpected concern about the potential for retinal toxicity that emerged from animal experiments.
A total of six individuals received the antibody, and two showed clear evidence of increased HIV Gag-specific CD8 T cell responses (measured both by interferon gamma production and expression of CD107a, a marker of cytotoxicity), but the overall average change compared to a control group of two placebo recipients did not reach statistical significance. An assay that can measure HIV RNA levels down to a single copy did not reveal significant changes associated with the treatment, but one individual experienced a tenfold decline in levels of cell-associated HIV RNA, and Eron noted that this was the person who experienced the greatest increase in Gag-specific CD8 T cell responses. This individual also had the highest baseline expression of PD-1, hinting that perhaps they had started with the most exhausted HIV-specific T cell response and were therefore best able to respond to the antibody.
In terms of safety, no evidence of the retinal toxicity that stymied plans to escalate dosing was observed. However, one person developed autoimmune pituitary insufficiency nine months after the infusion, and, although the relationship to the anti-PD-L1 antibody is uncertain, the fact that it was an autoimmune phenomenon raises serious concerns about whether further studies of antibodies targeting the PD-1 pathway will be possible in otherwise healthy HIV-positive people.
An alternate approach to investigating immune checkpoint inhibition in HIV is to conduct trials limited to HIV-positive individuals with cancers that are unresponsive to standard therapies, and this is the tack that has been taken by Thomas Uldrick at the National Cancer Institute. The primary goal of Uldrick's phase I study of the anti-PD-1 antibody pembrolizumab is to assess whether the cancers can be successfully treated, but secondary analyses will measure the effect on the HIV reservoir and HIV-specific immune responses.
Lakshmi Rajdev of the AIDS Malignancy Consortium at the National Cancer Institute is conducting a multicenter trial of a combination of the anti-CTLA-4 antibody ipilimumab with the anti-PD-1 antibody nivolumab in HIV-positive people with advanced, HIV-associated solid tumors that are refractory to standard care. The primary endpoint is safety, but the study will also look at efficacy against cancer and several HIV-related parameters, including viral load and HIV-specific T cell immunity.
Another potential source of information is case reports on HIV-positive people with cancer who have received approved immune checkpoint inhibitors as part of their medical care. One such report has been published on an individual with HIV and metastatic melanoma who received the anti-CTLA-4 antibody ipilimumab and, interestingly, there was evidence of transient increases in cell-associated HIV RNA after infusions, suggestive of latency-reversing activity.27 In parallel, HIV RNA levels measured by a single copy assay declined over time, from 60 to 5 copies/ml. The report has spurred interest in conducting further research, but it is currently uncertain whether ipilimumab can be studied outside of the cancer setting; results from other ongoing trials and experiments in animal models should help to ascertain if this will be possible.
The company Calimmune is also pursuing a strategy involving gene modification of stem cells. Their approach uses a lentiviral vector designed to both downregulate CCR5 expression and introduce a gene that encodes an HIV fusion inhibitor, designated C46.29 Results are pending from an ongoing phase I trial in the U.S., and recruitment began earlier this year for another small study in Australia that is being conducted by Anthony Kelleher at the Kirby Institute.
A possible gene therapy candidate that has generated intense interest recently involves the use of the gene-editing tool CRISPR/Cas9 to try and excise the HIV genome from latently infected cells. CRISPR/Cas9 is derived from bacteria, where it evolved as a defense mechanism against invading viruses. Researchers have reported some success in using CRISPR/Cas9 to delete HIV genes from cells30 and small animals31 in laboratory studies, but it has also emerged that viruses can rapidly become resistant to its effects.32,33,34 Although some scientists have made optimistic predictions that human trials may begin in the next few years, it is not yet known whether it will be feasible to deliver CRISPR/Cas9 into the human body.
Ruxolitinib is an FDA-approved treatment for myelofibrosis (a type of bone marrow cancer) that targets a cellular signaling pathway with a complicated name: the Janus activating kinase–signal transducer and activator of transcription (JAK-STAT) pathway. Studies have shown that this pathway is activated in HIV-infected macrophages and lymphocytes, creating an inflammatory environment that favors viral replication and persistence.35,36 In laboratory experiments, ruxolitinib countered this environment and inhibited HIV,37 leading researchers at the National Institute of Allergy and Infectious Diseases (NIAID) to launch a clinical trial of the drug in individuals on ART. Endpoints include safety, anti-inflammatory activity, and impact on the HIV reservoir.
The question of whether suppressing inflammation can reduce the HIV reservoir is being probed in several other studies. At the University of California, San Francisco, Priscilla Hsue and colleagues are testing canakinumab, an antibody that blocks the inflammatory cytokine interleukin-1β (IL-1β), primarily to assess whether it can beneficially modulate markers of cardiovascular disease risk, but measures of the HIV reservoir are among the secondary endpoints.
CC-11050 is a novel compound that inhibits phosphodiesterase-4; other drugs in this class have been found to be useful against inflammatory diseases such as asthma and psoriasis.38 Researchers at NIAID have initiated a study to evaluate CC-11050 in HIV-positive individuals on ART, including any effects on HIV persistence.
Jean-Pierre Routy and colleagues at McGill University in Canada are investigating the antidiabetic drug metformin, which has recently been shown to also have an anti-inflammatory mechanism of action.39 The primary goal of the trial, named the Lilac Study, is to measure if the drug reduces the size of the HIV reservoir.
The monoclonal antibody vedolizumab is an FDA-approved treatment for ulcerative colitis and Crohn's disease. It binds to a molecule expressed on CD4 T cells, α4β7 integrin, that is involved in the trafficking of cells to the gut. As there is evidence that HIV can interact with the α4β7 integrin in a manner that enhances transmission and viral replication,40,41 researchers at NIAID are on the verge of initiating a trial that will evaluate whether vedolizumab administration can suppress viral load during an ART interruption. The approach has shown activity in the SIV/macaque model,42 but some laboratory experiments have suggested that the capacity to bind to the α4β7 integrin is uncommon among HIV isolates;43 the NIAID study should reveal whether there is a relationship between HIV and α4β7 integrins that can be targeted therapeutically.
Many laboratory studies have identified PKC agonists as having the potential to reverse HIV latency.44,45 Recently, results of the first human trial of the PKC agonist bryostatin-1 were published, demonstrating that a single, low dose of the drug appears to be safe in individuals on ART, but the study did not show activity against the latent HIV reservoir.46 The researchers now aim to explore the effects of multiple doses and combinations with other candidate LRAs.
Sulggi Lee and colleagues at the University of California, San Francisco are hoping to soon launch a trial of a plant extract used in traditional Chinese medicine, kansui, on the basis that it contains PKC agonists with latency-reversing activity known as ingenols.47 The product is delivered as a tea made from powder extracted from the plant Euphorbia kansui.
At CROI 2016, two presentations debuted data from trials of the bNAb VRC01 in HIV-positive people undergoing ART interruptions. Katherine Bar from the University of Pennsylvania described results from a trial involving three infusions of VRC01, given before and after an interruption of ART to assess whether viral load rebound would be delayed.50 The antibody was safe and well tolerated, but there was only a slight hint of a short-term delay in the return of detectable viral load compared with historical controls, which evanesced by eight weeks of post-interruption follow up. Bar highlighted the need to better understand the relationship between HIV neutralization measured in laboratory assays and antibody potency in people, and suggested that combinations of different bNAbs will likely be required to improve results. Another similar trial conducted by Tae-Wook Chun at the NIAID was presented at CROI 2016 as a poster, reporting broadly consistent findings.51 Results from several trials of newer bNAbs that appear to be more potent than VRC01 are pending.
Several years ago there was a wave of media coverage regarding a study suggesting that ciclopirox, an antifungal drug, or deferiprone, an iron chelator that is used to treat thalassemia, might be able to promote the apoptotic death of HIV-infected cells.52 In May of 2016, results of a small pilot trial of deferiprone in ART-naive HIV-positive people in South Africa were published, claiming evidence of mild antiretroviral activity in a small number of individuals with deferiprone levels above a certain threshold.53 A variety of side effects were also reported, including elevations in transaminases and serum liver enzymes, and over a third of participants assigned to the highest dose did not complete the study. The researchers nevertheless continue to investigate the approach, and a second, larger trial—also conducted in South Africa—is now in follow up.
As explained in the introduction, the pursuit of immune-based adjuncts to ART now represents a small niche in the HIV research portfolio with essentially no significant industry interest. Much of the work in this area involves probiotic supplements, which are available over the counter, but are typically expensive, and, despite some evidence of beneficial effects, the data are unfortunately insufficient to offer a great deal of guidance as to how best they might be used.
Over the past year, two additional probiotic studies have been published that appear somewhat consistent with findings from a randomized trial of Saccharomyces boulardii54 that was described in the 2015 Pipeline Report. Birgitte Stiksrud and colleagues from Oslo University Hospital in Norway conducted a small trial of multistrain probiotics delivered in the form of fermented skimmed milk supplemented with Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis B-12 and Lactobacillus acidophilus. A total of 32 HIV-positive people on ART with CD4 T cell counts below 500 participated and were randomly assigned to receive the intervention (15), placebo (9), or to serve as untreated controls (8). After eight weeks, a significant 33% decline in levels of D-dimer—a coagulation biomarker that is associated with risk of mortality55—was observed, along with falls in levels of the inflammatory biomarkers C-reactive protein and IL-6, which did not quite crest the threshold for statistical significance.
The second study was performed by Gabriella d'Ettorre and colleagues from the University of Rome, and administered a probiotic containing Streptococcus salivarius ssp. Termophilus, Bifidobacteria represented by B. breve, B. infantis, and B. longum, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus delbrueckii ssp. Bulgaricus, and Streptococcus faecium. The supplement was taken for 48 weeks, twice a day. A total of 20 HIV-positive participants on suppressive ART were enrolled together with 11 HIV-negative controls. The researchers documented significant declines in levels of immune activation markers on CD4 T cells, high-sensitivity C-reactive protein and lipopolysaccharide binding protein (LBP). In contrast to the Norwegian study, D-dimer levels did not change significantly.
The reason for listing the multifarious species of bacteria used in these trials is to highlight the daunting complexity that lies behind the deceptively simple term probiotic. With relatively little else on offer to address the residual inflammation and immune activation that can persist despite ART, there is a need to try and pull together the scattered data suggesting that probiotics could be helpful and to design research that could provide clear guidance as to how best they might be used. TAG's recommendation is that a research funder—perhaps the Bill & Melinda Gates Foundation, who are co-sponsoring an ongoing trial of the probiotic VSL#3 in HIV-positive individuals—convene a workshop for investigators to generate a scientific agenda for resolving uncertainties about the value of probiotics as adjuncts to ART.
The expansion of clinical research into curing HIV infection continues in 2016; seen in light of Mao's view on the benefits of many blooming flowers, this offers reasons for optimism that encouraging data is likely to emerge from at least some trials. A counterbalancing cause for caution is that, thus far, the HIV reservoir that persists despite ART is proving stubbornly difficult to reduce. The latest news on the state of the field can be expected to emerge from the IAS Towards an HIV Cure Symposium that will take place in Durban, South Africa, July 16–17, and the NIH-sponsored Strategies for an HIV Cure workshop, which is scheduled for November 14–16 in Bethesda, Maryland, U.S.A.
Efforts to develop immune-based enhancements to ART remain on the backburner, at least relatively speaking. But activists and researchers are seeking ways to ensure that the work carries on, as there is evidence that an effective intervention could address residual risks of morbidity and mortality, particularly in immunologic non-responders. It is possible that the strategies being studied in the context of curing HIV will turn out to have potential as additions to ART, and it is important that results from trials are viewed with this possibility in mind to avoid potential therapies being discarded prematurely.
Unless noted otherwise, all links were accessed on June 7, 2016.
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Andrés C, Plana M, Guardo AC, et al. HIV-1 Reservoir Dynamics after Vaccination and Antiretroviral Therapy Interruption Are Associated with Dendritic Cell Vaccine-Induced T Cell Responses. J Virol. 2015 Sep;89(18):9189–99. doi: 10.1128/JVI.01062-15.
Jones RB, Kovacs C, Chun TW, Ostrowski MA. Short communication: HIV type 1 accumulates in influenza-specific T cells in subjects receiving seasonal vaccination in the context of effective antiretroviral therapy. AIDS Res Hum Retroviruses. 2012 Dec;28(12):1687–92. doi: 10.1089/AID.2012.0115.
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Day CL, Kaufmann DE, Kiepiela P, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006 Sep 21;443(7109):350–4. doi: 10.1038/nature05115.
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Chew GM, Fujita T, Webb GM, et al. TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection. PLoS Pathog. 2016 Jan 7;12(1):e1005349. doi: 10.1371/journal.ppat.1005349.
Fromentin R, DaFonseca S, Bakeman W, et al. The Immune Checkpoint Blockers PD-1 LAG-3 and TIGIT are Associated With HIV Persistence During ART (Abstract 412). Paper presented at: 21st CROI; 2014 March 3–6; Boston MA. Available from: http://www.croiconference.org/sessions/immune-checkpoint-blockers-pd-1-lag-3-and-tigit-are-associated-hiv-persistence-during-art.
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Cannon PM. Progress in Gene Therapy for HIV Cure (Abstract 78). Paper presented at: 23rd CROI; 2016 February 22–25; Boston, MA. Available from: http://www.croiwebcasts.org/console/player/29574?mediaType=audio&.
Wolstein O, Boyd M, Millington M, et al. Preclinical safety and efficacy of an anti-HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor. Mol Ther Methods Clin Dev. 2014 Feb 12;1:11. doi: 10.1038/mtm.2013.11.
Kaminski R, Chen Y, Fischer T, et al. Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing. Sci Rep. 2016 Mar 4;6:22555. doi: 10.1038/srep22555.
Wang Z, Pan Q, Gendron P, et al. CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape. Cell Rep. 2016 Apr 19;15(3):481–9. doi: 10.1016/j.celrep.2016.03.042.
Liang C, Wainberg MA, Das AT, Berkhout B. CRISPR/Cas9: a double-edged sword when used to combat HIV infection. Retrovirology. 2016 May 27;13(1):37. doi: 10.1186/s12977-016-0270-0.
Kohler JJ, Tuttle DL, Coberley CR, Sleasman JW, Goodenow MM. Human immunodeficiency virus type 1 (HIV-1) induces activation of multiple STATs in CD4+ cells of lymphocyte or monocyte/macrophage lineages. J Leukoc Biol. 2003 Mar; 73(3):407–16. doi: 10.1189/jlb.0702358.
Chaudhuri A, Yang B, Gendelman HE, Persidsky Y, Kanmogne GD. STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier. Blood. 2008 Feb 15; 111(4):2062–72. doi: 10.1182/blood-2007-05-091207.
Gavegnano C, Detorio M, Montero C, Bosque A, Planelles V, Schinazi RF. Ruxolitinib and tofacitinib are potent and selective inhibitors of HIV-1 replication and virus reactivation in vitro. Antimicrob Agents Chemother. 2014;58(4):1977–86. doi: 10.1128/AAC.02496-13.
Azam M.A., Tripuraneni N.S. Selective phosphodiesterase 4B inhibitors: a review. Sci Pharm. 2014 Jun 10;82(3):453–81. doi: 10.3797/scipharm.1404-08.
Saisho Y. Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect. Endocr Metab Immune Disord Drug Targets. 2015;15(3):196–205. doi: 10.2174/1871530315666150316124019.
Arthos J, Cicala C, Martinelli E, et al. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008 Mar;9(3):301–9. doi: 10.1038/ni1566.
Cicala C, Martinelli E, McNally JP, et al. The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20877–82. doi: 10.1073/pnas.0911796106.
Ansari AA, Reimann KA, Mayne AE, et al. Blocking of α4β7 gut-homing integrin during acute infection leads to decreased plasma and gastrointestinal tissue viral loads in simian immunodeficiency virus-infected rhesus macaques. J Immunol. 2011 Jan 15;186(2):1044–59. doi: 10.4049/jimmunol.1003052.
Perez LG, Chen H, Liao HX, Montefiori DC. Envelope glycoprotein binding to the integrin α4β7 is not a general property of most HIV-1 strains. J Virol. 2014 Sep;88(18):10767–77. doi: 10.1128/JVI.03296-13.
Jiang G, Dandekar S. Targeting NF-κB signaling with protein kinase C agonists as an emerging strategy for combating HIV latency. AIDS Res Hum Retroviruses. 2015 Jan;31(1):4–12. doi: 10.1089/AID.2014.0199.
Gutiérrez C, Serrano-Villar S, Madrid-Elena N, et al. Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy. AIDS. 2016 Jun 1;30(9):1385–92. doi: 10.1097/QAD.0000000000001064.
Poveda E. Ingenol derivates promising for HIV eradication. AIDS Rev. 2014 Oct-Dec;16(4):246.
Bournazos S, Klein F, Pietzsch J, Seaman MS, Nussenzweig MC, Ravetch JV. Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell. 2014 Sep 11;158(6):1243–53. doi: 10.1016/j.cell.2014.08.023.
Halper-Stromberg A, Nussenzweig MC. Towards HIV-1 remission: potential roles for broadly neutralizing antibodies. J Clin Invest. 2016 Feb;126(2):415–23. doi: 10.1172/JCI80561.
Bar KJ, Harrison LJ, Overton ET, et al. ACTG 5340:The Effect of VRC01 on Viral Kinetics After Analytic Treatment Interruption (Abstract 32LB). Paper presented at: 23rd CROI; 2016 February 22–25; Boston, MA. Available from: http://www.croiwebcasts.org/console/player/29460?mediaType=audio&.
Chun TW, Sneller M, Seamon C, et al. Effect of Infusion of Broadly Neutralizing Antibody VRC01 on HIV Plasma Rebound (Abstract 311LB). Paper presented at: 23rd CROI; 2016 February 22–25; Boston, MA. Available from: http://www.croiconference.org/sites/default/files/posters-2016/311LB.pdf.
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Saxena D, Spino M, Tricta F, et al. Drug-Based Lead Discovery: The Novel Ablative Antiretroviral Profile of Deferiprone in HIV-1-Infected Cells and in HIV-Infected Treatment-Naive Subjects of a Double-Blind, Placebo-Controlled, Randomized Exploratory Trial. PLoS One. 2016 May 18;11(5):e0154842. doi: 10.1371/journal.pone.0154842.
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text:
Short Film: The Last Word
I think I end up saying this all the time these days, but sorry to you faithful dudes about the lack of updates around here. As I said before, there's just not a whole lot to update on at the moment. Everyone's kind of doing their own thing, and whether that turns into a Smooth Few Films project in the near future is anyone's guess.
For instance, I've been working on a monster of a book which I just finished in this past week. It's a huge unwieldy fantasy story that needs a ton of editing that I can't wait to get started on. Meanwhile, Daniel recently produced a short film with his bud Ryan Hargrave for a local art show. It's called The Last Word, and I kind of love it. Different from the tone that you guys are used to from Daniel's work to be sure, but that's not a bad thing.
You'll notice a few SFF regulars in there, including Alex, who played Pedro in WZ and also ran sound for that series as well. You'll also see Ty, the lovable Bobby King. Music by Jace Ford, in what I think is one of his best pieces yet. Plus, Daniel plays a dude that chases people and beats them up. Anyway, take a gander to see what I mean, and give Daniel his props.
Another TLW soundtrack song coming next week!
This entry was posted in Extras, film, News, Web Zeroes and tagged short film, the last word on October 30, 2010 by Eddy.
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13 thoughts on "Short Film: The Last Word"
Kamran Nikhad October 30, 2010 at 2:35 am
Truly remarkable work.
I love the contrast behind each scene, and just how down to earth each one is. Look around, these things are happening all the time, for some folks, just trying to walk home can be a dangerous trek, sometimes never opening up with the people you love can compromise everything, and sometimes just not allowing yourself to reach others can create a world of loneliness, which as the man at the bar proved, can worsen to self destruction in more ways than one.
The performance and display shown from each actor stuck in each scenario was just so spot on, their body language, their actions, it was just brilliant direction.
And of course, the counter-act of each scenario really does show how much going the extra mile, however simple it can be from simply opening yourself to new people, you can in turn make great friends and shed a lot more light on ones life. To owning up to your mistakes, allowing the person you care about trust you enough to make it work, no matter how rough the relationship. All the way down to standing up for those in need. Sometimes it really embodies the strength we all wish we had, and other times, we can surprise ourselves. I feel that the message was visually and emotionally very human, and something we, as viewers, and as members of society really do need to reach down and own up to.
For that, I say truly excellent work, Daniel and company, you guys have made a truly outstanding short here.
hypnotek October 30, 2010 at 1:08 pm
Beautiful piece of work my boys. Simply beautiful.
f4741 3rr0r October 31, 2010 at 8:13 am
It is always nice to see what you guys are working on. Keep up the excellent work.
Kratos October 31, 2010 at 9:05 am
Really nice video, does anybody knnow where I can download the song that they used or created?
StaleThesis October 31, 2010 at 5:04 pm
Cool video. Jace always makes the best music. Where do i get it?
moorsey November 1, 2010 at 1:12 pm
wow, just speechless, that was so so beautiful, awesome, really awesome. Perfect music with every scene, I even have man tears after the last scene.
That was Bobby King by the way? What a difference a tash makes!
Jenn November 4, 2010 at 3:11 am
This Is a Work of Art, I almost wanted to end badly to show how life is. I actually Cried for the couple knowing and feel that pain. Bobby King Was Amazing just Stunting, he look fantastic in it. Wow! The Bar scene could of done a little better, i didn't under stand it until the phone part until the end seeing him rejecting the phone call with a name would of been more understand and It would of been cool if some one just came up and ask him to hang out, a more personal feeling. But feeling the bar guy loneliness came across perfectly.
I definitely got my heart into itl.
glebe November 4, 2010 at 7:42 pm
That was awesome. Outstanding work, Daniel, Pedro, Ty and Jace.
fsdetained November 5, 2010 at 12:55 pm
Beautiful. I can't think of any better way to describe it. Acting and music as great as always.
You know she was leaving Ty because he got rid of the 'stache 😛
Pfhortipfhy November 13, 2010 at 11:29 pm
Hey there. I'm wondering, what with the store down and all, if it's still possible to obtain the soundtrack?
Also, great work on the film, Daniel! I miss you guys- I loved your stuff.
nelandquinten November 15, 2010 at 10:17 pm
Nice work Daniel!
Hey, in the description, you said that Alex played Pedro in WZ. Don't you mean the Leet World?
Eddy November 16, 2010 at 12:30 am
Nope. There was a Pedro in WZ. Pedro and Scott, Alex's co-workers.
Tarik February 4, 2011 at 3:37 am
I am in europe, will there be a very high price on the sound track when I buy it over here? (my main concern would be shipping of course)


JACQUELINE C. MORBY joined TA Associates in 1978. She was a managing director of TA Associates from 1982 to 2002, serving on the firm's four-member executive committee from 1988 to 2001. In 2003, she retired but continued to play an active role as senior advisor to the firm. Formed in 1968, TA Associates, operating from offices in Boston, Menlo Park, London, Mumbai and Hong Kong, manages $15 billion of private equity growth capital. The firm invests in a wide variety of technology and service industries. Morby graduated from Stanford University with a bachelor of arts degree in psychology and from the Simmons Graduate Management School with an MBA. She has served as a director of the following public companies: Ansy, Inc., Axent Technologies, Inc., BMC Software, Inc., Boron, LePore & Associates, Inc., Ontrack Computer Systems, Inc., Econometry Corporation, System Software Associates, Sierra On-Line, Inc., AI Corp and PacificLife Corporation. She currently serves on the board of trustees of the Andy Warhol Museum, and on the boards of directors of Lead Pittsburgh and Population Action International. Ten years ago she and her husband, Jeffrey Morby, co-founded the Cure Alzheimer's Fund, a venture philanthropy 501c3 foundation that supports leading edge Alzheimer's research.


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redpajama_set_name: RedPajamaGithub


U.S. Immigration and Customs Enforcement is experimenting with some new and innovative techniques in procurement — an effort to make the process quicker and easier to understand for vendors, especially smaller businesses.
The techniques aim at streamlining source selection, the stage of certain kinds of government procurement when possible vendors are assessed, ranked and sometimes whittled down, explained Sarah Todd, Deputy Head of Contracting Activity in ICE's Office of Acquisition Management.
"All of these [innovations] are driving towards shorter lead times from the time we get a proposal or a quotation until we can make that award," she told attendees at a recent GTSC event. The changes mean that "Things could move a lot faster than we have typically moved in the past," on procurements, she said.
The two stage approach will allow acquisition officials to inform vendors closer to the start of the process, that they're unlikely to reach the finish line. After receiving and evaluating initial proposals, officials will rate them, Todd said.
"For the folks that are not among the highest rated, you will get a little note from us that says, 'Hey, at this time you're not among the highest rated for this procurement,'" she explained. Since officials will end up choosing between proposals from the highest rated vendors, those not in that top tier might want to think about cutting their losses before ploughing more resources into submitting a proposal in the second stage.
But it's completely voluntary, hence not a true down select, but rather an advisory one.
"You can … decide whether or not you want to move into the second phase, and you're welcome to do that, but if you don't think that you're going to be able to make significant improvements, to get yourself into that higher rating, you might want think about saving those proposal dollars" by not moving ahead, Todd said.
"I think that's really helpful for industry and for us, because then vendors have more information about their chances for award and we're likely evaluating fewer proposals in the second phase", she explained to HS Today in an interview after her talk.
Secondly, she said the agency is experimenting with changing the way it classifies vendors technical proposals. Traditionally officials break them down into five categories: Excellent, good, acceptable, marginal and unacceptable. The definitions of how a vendor gets into one of those categories can be convoluted.
For instance, to be rated "excellent" a proposal may just need to be free of any weaknesses, Todd noted. "Our adjectival ratings are not always differentiating in a really useful way to perform a transparent tradeoff," she acknowledged.
Under the new system, officials would break down rated proposals into three categories: High confidence, confident or low confidence. Todd said this "simpler evaluation scheme" would better reflect the fact that a range of proposals end up in each category — and make it easier to explain to vendors why officials made the choices they did.
"This is all about making sure we know what it is we're evaluating … but also being able to give better feedback to you," she told the audience of GTSC members and other vendors.
"It gives us a little more flexibility and makes the process easier to understand for vendors," she told HS Today afterwards, noting these innovations had been piloted by the DHS Chief Procurement Officer's Procurement Innovation Lab.
Finally, she said, the agency was also experimenting with its internal procedures, to do more face to face and on the spot evaluation, in order to avoid the often drawn-out process of aligning different officials' submissions.
"We're streamlining our paperwork," she said.


The story is set in Boston and begins in the 1970's. Toby and Elizabeth meet at the park while there with their children and form a lifetime friendship. Toby who is an avid reader is given a book by Elizabeth called "Trolley Girl" and hence begins the "bookception" if you will, a book-within-a-book.
"Trolley Girl" is made to believe it's based on a true account of a union activist in the 1920's in Boston. It tells her story of tragic events that changes the lives her she and her family.
I felt the character development in this story was superb. Toby and Elizabeth's friendship spans the decades from when their children are infants until they are grown. Definitely one of the best books I've read about a friendship. It was believable and palpable.
As I began this book I found it difficult to follow due to the unusual dialogue construction. Fighting it at first it was beyond frustrating but once I grew accustomed to this style it became easier to follow. I would recommend this a book to a true reader. Someone who loves reading simply for the sake of reading.


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    /**
     *

     * The version of the rule group. You can only use a version that is not scheduled for expiration. If you don't
     * provide this, WAF uses the vendor's default version.
     *

     */
    private String versionName;

    /**
     *

     * The name of the managed rule group vendor. You use this, along with the rule group name, to identify the rule
     * group.
     *

     *
     * @param vendorName
     *        The name of the managed rule group vendor. You use this, along with the rule group name, to identify the
     *        rule group.
     */

    public void setVendorName(String vendorName) {
        this.vendorName = vendorName;
    }

    /**
     *

     * The name of the managed rule group vendor. You use this, along with the rule group name, to identify the rule
     * group.
     *

     *
     * @return The name of the managed rule group vendor. You use this, along with the rule group name, to identify the
     *         rule group.
     */

    public String getVendorName() {
        return this.vendorName;
    }

    /**
     *

     * The name of the managed rule group vendor. You use this, along with the rule group name, to identify the rule
     * group.
     *

     *
     * @param vendorName
     *        The name of the managed rule group vendor. You use this, along with the rule group name, to identify the
     *        rule group.
     * @return Returns a reference to this object so that method calls can be chained together.
     */

    public DescribeManagedRuleGroupRequest withVendorName(String vendorName) {
        setVendorName(vendorName);
        return this;
    }

    /**
     *

     * The name of the managed rule group. You use this, along with the vendor name, to identify the rule group.
     *

     *
     * @param name
     *        The name of the managed rule group. You use this, along with the vendor name, to identify the rule group.
     */

    public void setName(String name) {
        this.name = name;
    }

    /**
     *

     * The name of the managed rule group. You use this, along with the vendor name, to identify the rule group.
     *

     *
     * @return The name of the managed rule group. You use this, along with the vendor name, to identify the rule group.
     */

    public String getName() {
        return this.name;
    }

    /**
     *

     * The name of the managed rule group. You use this, along with the vendor name, to identify the rule group.
     *

     *
     * @param name
     *        The name of the managed rule group. You use this, along with the vendor name, to identify the rule group.
     * @return Returns a reference to this object so that method calls can be chained together.
     */

    public DescribeManagedRuleGroupRequest withName(String name) {
        setName(name);
        return this;
    }

    /**
     *

     * Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     * application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL API, or
     * an Amazon Cognito user pool.
     *

     *

     * To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     * CLI - Specify the Region when you use the CloudFront scope: --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     * API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     *

     *
     * @param scope
     *        Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     *        application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL
     *        API, or an Amazon Cognito user pool.

     *

     *        To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     *        CLI - Specify the Region when you use the CloudFront scope:
     *        --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     *        API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     * @see Scope
     */

    public void setScope(String scope) {
        this.scope = scope;
    }

    /**
     *

     * Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     * application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL API, or
     * an Amazon Cognito user pool.
     *

     *

     * To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     * CLI - Specify the Region when you use the CloudFront scope: --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     * API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     *

     *
     * @return Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     *         application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL
     *         API, or an Amazon Cognito user pool.

     *

     *         To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     *         CLI - Specify the Region when you use the CloudFront scope:
     *         --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     *         API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     * @see Scope
     */

    public String getScope() {
        return this.scope;
    }

    /**
     *

     * Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     * application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL API, or
     * an Amazon Cognito user pool.
     *

     *

     * To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     * CLI - Specify the Region when you use the CloudFront scope: --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     * API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     *

     *
     * @param scope
     *        Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     *        application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL
     *        API, or an Amazon Cognito user pool.

     *

     *        To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     *        CLI - Specify the Region when you use the CloudFront scope:
     *        --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     *        API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     * @return Returns a reference to this object so that method calls can be chained together.
     * @see Scope
     */

    public DescribeManagedRuleGroupRequest withScope(String scope) {
        setScope(scope);
        return this;
    }

    /**
     *

     * Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     * application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL API, or
     * an Amazon Cognito user pool.
     *

     *

     * To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     * CLI - Specify the Region when you use the CloudFront scope: --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     * API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     *

     *
     * @param scope
     *        Specifies whether this is for an Amazon CloudFront distribution or for a regional application. A regional
     *        application can be an Application Load Balancer (ALB), an Amazon API Gateway REST API, an AppSync GraphQL
     *        API, or an Amazon Cognito user pool.

     *

     *        To work with CloudFront, you must also specify the Region US East (N. Virginia) as follows:
     *

     *

     *

     *

     *        CLI - Specify the Region when you use the CloudFront scope:
     *        --scope=CLOUDFRONT --region=us-east-1.
     *

     *

     *

     *

     *        API and SDKs - For all calls, use the Region endpoint us-east-1.
     *

     *

     * @return Returns a reference to this object so that method calls can be chained together.
     * @see Scope
     */

    public DescribeManagedRuleGroupRequest withScope(Scope scope) {
        this.scope = scope.toString();
        return this;
    }

    /**
     *

     * The version of the rule group. You can only use a version that is not scheduled for expiration. If you don't
     * provide this, WAF uses the vendor's default version.
     *

     *
     * @param versionName
     *        The version of the rule group. You can only use a version that is not scheduled for expiration. If you
     *        don't provide this, WAF uses the vendor's default version.
     */

    public void setVersionName(String versionName) {
        this.versionName = versionName;
    }

    /**
     *

     * The version of the rule group. You can only use a version that is not scheduled for expiration. If you don't
     * provide this, WAF uses the vendor's default version.
     *

     *
     * @return The version of the rule group. You can only use a version that is not scheduled for expiration. If you
     *         don't provide this, WAF uses the vendor's default version.
     */

    public String getVersionName() {
        return this.versionName;
    }

    /**
     *

     * The version of the rule group. You can only use a version that is not scheduled for expiration. If you don't
     * provide this, WAF uses the vendor's default version.
     *

     *
     * @param versionName
     *        The version of the rule group. You can only use a version that is not scheduled for expiration. If you
     *        don't provide this, WAF uses the vendor's default version.
     * @return Returns a reference to this object so that method calls can be chained together.
     */

    public DescribeManagedRuleGroupRequest withVersionName(String versionName) {
        setVersionName(versionName);
        return this;
    }

    /**
     * Returns a string representation of this object. This is useful for testing and debugging. Sensitive data will be
     * redacted from this string using a placeholder value.
     *
     * @return A string representation of this object.
     *
     * @see java.lang.Object#toString()
     */
    @Override
    public String toString() {
        StringBuilder sb = new StringBuilder();
        sb.append("{");
        if (getVendorName() != null)
            sb.append("VendorName: ").append(getVendorName()).append(",");
        if (getName() != null)
            sb.append("Name: ").append(getName()).append(",");
        if (getScope() != null)
            sb.append("Scope: ").append(getScope()).append(",");
        if (getVersionName() != null)
            sb.append("VersionName: ").append(getVersionName());
        sb.append("}");
        return sb.toString();
    }

    @Override
    public boolean equals(Object obj) {
        if (this == obj)
            return true;
        if (obj == null)
            return false;

        if (obj instanceof DescribeManagedRuleGroupRequest == false)
            return false;
        DescribeManagedRuleGroupRequest other = (DescribeManagedRuleGroupRequest) obj;
        if (other.getVendorName() == null ^ this.getVendorName() == null)
            return false;
        if (other.getVendorName() != null && other.getVendorName().equals(this.getVendorName()) == false)
            return false;
        if (other.getName() == null ^ this.getName() == null)
            return false;
        if (other.getName() != null && other.getName().equals(this.getName()) == false)
            return false;
        if (other.getScope() == null ^ this.getScope() == null)
            return false;
        if (other.getScope() != null && other.getScope().equals(this.getScope()) == false)
            return false;
        if (other.getVersionName() == null ^ this.getVersionName() == null)
            return false;
        if (other.getVersionName() != null && other.getVersionName().equals(this.getVersionName()) == false)
            return false;
        return true;
    }

    @Override
    public int hashCode() {
        final int prime = 31;
        int hashCode = 1;

        hashCode = prime * hashCode + ((getVendorName() == null) ? 0 : getVendorName().hashCode());
        hashCode = prime * hashCode + ((getName() == null) ? 0 : getName().hashCode());
        hashCode = prime * hashCode + ((getScope() == null) ? 0 : getScope().hashCode());
        hashCode = prime * hashCode + ((getVersionName() == null) ? 0 : getVersionName().hashCode());
        return hashCode;
    }

    @Override
    public DescribeManagedRuleGroupRequest clone() {
        return (DescribeManagedRuleGroupRequest) super.clone();
    }

}


American citizenship is something that millions of people around the world dream about, while millions of those who were born in the United States automatically fulfilled this dream.
Most probably, you are also a happy American citizen who enjoys all the rights that this privileged status gives. Yet, what exactly do you know about your rights? Another question is – what do you know about your responsibilities as a citizen? Answering these questions seems to be a good starting point for those writing essays on citizenship.
What exactly should I write about?
How should my essay on memories be organized?
How will I captivate the reader?
Well, let us help you sort everything out and complete your essay on memories successfully.
You know that being late is bad, but you cannot do anything about this habit of yours. You are late to school, dates, buses, and it seems that you are going to be late with your written assignment.
By the way, this assignment was given specially to you. You are the only one in class who has to write an essay on being late. What an exclusive task! Yet, it seems like your teacher is tired of your irresponsibility (and this is exactly what he/she thinks about you).


One day, while stretching my client Jim, I was taken aback when I realized he wasn't wearing underwear. His shorts were swim trunks with interior netting. I quickly looked away and continued to stretch him. This happened with Jim on several other occasions, but I never mentioned it because I wasn't sure how to broach the matter. I also didn't feel that he was doing this intentionally, nor did I believe he meant harm.
While some may consider Jim's behavior a case of sexual harassment, at the time I didn't see it as anything more than a lapse in judgment by my client—and knowing this man, I still believe that. This was also well before the #MeToo movement came into the spotlight. While I felt that this incident fell into a gray area, other situations are much more black-and-white.
What would you do if you were in one of these situations? Do you still need to put a protocol in place for dealing with sexual harassment issues and allegations? Fitness professionals who have experience with this topic offer guidance, tips and support.
For more information on sexual harassment between employers and staff and tips on how to create a safe place, please see "Sexual Harassment and the Fitness Industry" in the online IDEA Library or in the July 2018 print edition of IDEA Fitness Journal). If you cannot access the full article and would like to, please contact the IDEA Inspired Service Team at 800-999-4332, ext. 7.


text:
Pioneers in the neighborhood: We are being awarded the "Orte der Arbeit" Saarland architecture prize
Christine Gottlieb Head of Corporate Design
19.11.2021 • 5 minutes reading time
Awarded by the Saarland Ministry of Economics every two years, this architectural prize focuses on the theme of "places of work" in 2021. The award highlights the role of design skills as a critical factor for economic success. It underlines the importance of a holistic understanding of design to develop forward-looking strategies and sustainable construction.
A holistic perspective, to be pioneering and economical without sacrificing aesthetic qualities — these are not only the selection criteria for the architecture award but also the cornerstones of our daily work at Ergosign. Our company headquarters reflects this aspiration for our actions in our workplace too.
At almost 2,000 square meters, built to the latest KfW efficiency building standard (KfW 55), Ergosign's new headquarters was unveiled at Europaallee 20a in Saarbrücken in 2018 — not far from Ergosign's first company headquarters from 2008 — with a ceremony followed by a party. On 18 November 2021, we proudly and gladly accepted the architecture award together with our architect, Mario Krämer, from architecture firm FloSundK.
We want to use the award as an opportunity to offer some insight into the design and realization of our company headquarters.
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Creating a "place of work" for a team that collaborates with customers and partners both flexibly and collaboratively was one of the challenges. At the same time, the building was also to become a place for shared experiences and events.
How does an architect approach a task like this?
"As an architect, I want to precisely understand the task at hand before I begin a draft. This involves getting to know the people that the building is for and internalizing the intention of the design. It's important to me to collect as much insight about the eventual users' everyday work, their experiences in the world of work up to this point and, most of all, suggestions as to what could be improved. A major benefit of this project was that we already knew the team and Ergosign's working methods well, due to designing the first building.
We see communication within the team, as well as externally as the most defining characteristic of Ergosign. A team that works together and that is in constant discussion – with one another, clients, and other businesses. The main design approach for the new headquarters included a large central room where the whole Ergosign family could come together."
"Architecture is good when it is perceived without having studied architecture."
"Another thing was clear too. The new Ergosign II building must make a bold statement in its external appearance. The almost black metal façade, with port holes on the sides, is reminiscent of a ship. The Ergosign steamer can only be accessed via a narrow jetty (in this case the consciously small entrance).
To me, architecture is good when you perceive it without having studied architecture. A building is welcome to polarize too. I think this aim has been achieved successfully with the Ergosign II building," says Mario Krämer, FloSundK.
South and east view of our office building (Source: FLOSUNDK architektur+urbanistik GmbH)
Ergosign was founded in 2000 as a pioneer of UX Design in Germany. Today, we are one of the largest digital agencies focusing on User Experience, and a market leader on the DACH market. The decision to choose a location in the Eurobahnhof district was made back in 2007.
A brief look back: what were things in the new "Quartier Eurobahnhof" district like in 2007? And why did we opt for this location twice?
"We were pioneers in the district too!" said founder and CEO Professor Dieter Wallach, laughing. "In 2007, we broke ground at the Eurobahnhof district — thereby driving the development of what is now a flourishing neighbourhood. FloSundK already designed our first company building, which was awarded the developer's prize by the Chamber of Architects in 2010. Our constant growth meant we needed more space for new team members shortly after moving in. Just one year after the move, additional rented space opposite in the QBUS building was not intended as a permanent solution.
By 2017, it was clear that we would build a new, larger company building — Ergosign II. Luckily, we didn't have to search for long. We quickly found our new building plot, also on Europaallee, just a few numbers down.
The location is unbeatable: very central and close to the city with plenty of options for our lunch breaks, great infrastructure and perfect connections to public transport. We even developed a solution for the rather tight parking situation with our app xPark xPark which makes it possible for everyone to drive to the office spontaneously and find a parking spot easily."
Ergosign was able to fall back on its own construction experience. There must be lots of learnings that were applied to the construction of the new, second company building?
"Absolutely! There's a lot that we have learned and done better this time," says Dieter. "Including that some ideas might sound impressive in a meeting and even on paper, but they're just not practical in everyday life. We discuss, call and Zoom a lot. We especially wanted a solution that would save us the effort of looking for a free meeting room. The first building had a "telephone cubicle". A square of sturdy red fabric secured to the ceiling with steel cables floated in the open-plan office. It contained a small workplace that offered sound insulation and privacy to make telephone calls. And it was a real visual highlight. Although it was sadly impractical in practice, so never used. We have learned from it. The new building has a "room within a room" as a telephone box in the large offices. Complete with windows, sound insulation and air conditioning, it can play host to ad hoc meetings — even when these conversations are not intended for everyone's ears."
Designing the perfect company building can be compared to our approach in UX projects surprisingly well. We typically begin our client projects with a research phase. Before a concept can be established, we accompany, observe and interview the eventual users to understand their needs and conclude requirements for the design concept from these. Designing our building without involving the users was unthinkable for us.
"Design balances user requirements, technology and economy."
"Design balances user requirements, technology and economy" is one of Dieter's guiding principles. Requirements can often contradict one another — a collaborative approach helps us find the optimal balance.
A team plans together. That sounds exciting and a little complicated.
What does "collaboration" mean when constructing a new company building?
Markus Schwetje explains, "it was exciting and very productive. We first founded internal task forces, with all departments and experience levels represented. Interim results were introduced and feedback collected. With the help of regular meetings and digital boards, the group developed ideas and specific suggestions that were then discussed with the architects.
Of course, the roughly 100 other team members at the Saarbrücken site were also constantly informed about the plans and, later, construction progress. We were actively involved in each phase of construction."
"We don't want open-plan offices"
What was the most significant change wanted by the team?
And would we do it again?
"There was a clear message: we don't want open-plan offices," says Christian Grieger, Head of Site at Saarbrücken. "Design and Development sit next to each other. Splitting up the space into offices with two to five people — depending on size — allows quiet yet still collaborative work and encourages the exchange of expertise. Even the introduction of temporary project offices proved popular.
We'd make the decision to move away from large open-plan offices again, any time!
Another requirement we realized was the design of dedicated creative rooms. Spaces to give the mind room for innovative ideas, far removed from utilitarian meeting room setups. Each room was designed to a particular theme by the employees themselves — from a markedly comfortable, cozy room with carpet and a velvet couch to an industrial look and even a room completely without technology and screens."
Creative room Ali Farka Toure and one of the many sitting bunks
From outside, the building is a real eye-catcher with its iconic look and feel. The dark metal facade, round port holes on the sides and the large window front facing the train station.
How did this unusual façade come about?
"The large window front is actually one of the key elements of Ergosign II's design concept. It reflects the importance of the building's communicative center that lies behind it. To an extent, the window front opens and illuminates the space where encounters as well as both formal and informal exchanges take place within the framework of Ergosign's human-centered work culture in the most obvious way," says Dr. Marcus Plach, co-founder and CEO along with Dieter.
"The dark metal façade and its irregularly arranged slats give the surface a softer or harder texture depending on the sunlight, creating a dynamic contrast to the dark, elegant overall impression. The association of the port holes, i.e. with an object that is constantly moving, is absolutely intended."
Ergosign II is not just impressive from outside. There's plenty going on indoors too. Let's take a look at the interior: what does the building look like inside? What makes it so special?
"In contrast to the exterior, I'd describe the interior as bright and friendly. When you enter the building, an open staircase leads upstairs while the light-flooded forum provides a warm welcome," explains Marie-Claire Harnasch enthusiastically.
Blick ins Treppenhaus und unsere große Küche
"The large room with open kitchen and stage is the heart and communicative center of the building. Plenty of seating invites you to chat with colleagues over a coffee or tea."
Each Friday, the forum is transformed into an event location. Everyone meets for a communal lunch and there is a Lunch & Learn talk on the stage, sometimes held by team members and sometimes by external speakers.
Stage in use, whether at the Group Focus Time or weekly Lunch & Learn
"I think it's great that these kinds of company rituals have impacted the building's architecture and that space has been created for them," continues Marie. "The company building's clear structure is emphasized. In my view, the symmetrical design and clear divisions have resulted in workplaces of equal quality for all employees. Unlike other office buildings, we don't have long, empty corridors leading to closed rooms. Instead, each floor has a different purpose at its core while additional offices are separated. I like to stretch my legs around the building and constantly bump into a colleague that might be sitting in one of the seating booths located in all of the building's heavy traffic areas.
"My personal highlight: our roof terrace!"
My personal highlight: our roof terrace! Lots of space, fresh air and a great view of Saarbrücken. Especially in spring and summer, it's a great place to take a lunch break or have a beer after work together."
" External calm and internal variety form the framework for this impressive place of work, on the successful implementation of which one can only congratulate the team of developer and architect. - Jury for the "Orte der Arbeit" Saarland architecture award 2021"
Events and communal experiences define Ergosign's company culture. That's why it was important to have sufficient space for events in the building.
They say all the best parties take place in the kitchen. Can our new building keep up with that?
"Communication, discussion and team spirit are essential to Ergosign's culture. And which is known to be the best place to chat and celebrate? That's right, the kitchen. Even at our roofing ceremony, a band played in our kitchen although there wasn't actually a kitchen in there at the time. Our new office building offers great options inside and out, from opening ceremonies to Christmas parties, conferences, Group Focus Time, and events with external guests. Everyone knows how important personal interaction is, especially since Coronavirus," says Christine Gottlieb, who is responsible for coporate communication and events.
Our housewarming party 2018
Good communication needs good acoustics, whether in a meeting, at a talk, or listening to live music. Acoustics played a vital role in our interior design, which was a particular challenge in the forum. Extensive 3D models were used to calculate reverberation time and absorption to ensure that speech can always be heard clearly, everywhere in the long, tall room. The results flowed into the conception of the acoustically effective wooden cladding as well as stage and sound technology. The wood also creates a harmonious balance between steel, glass and concrete.
Fun fact #instafam: the building is regularly used as a focal point for private Instagram photo shoots.
What was your favorite moment?
"Groups of mostly young women in front of the windows can distract some people from their work," says Anna Polzin of her spot directly in the window on the ground floor. "From checking their makeup in the glass to that ever-popular duck face to sneaker product shoots — it never gets boring! The blinds are a welcome shield to stop you from becoming an unwilling internet star."
Our resume
Technological change is not an autonomous process — people design it.
A place of work should support people and add to their daily lives, just like digitization. Successful, sustainable change requires a pioneering spirit, a holistic perspective, collaboration and good partners.
Being awarded the architecture prize underlines our values, to which we will continue to remain true in the future.
We would like to thank Mario, Jens, the whole FloSundK architektur + urbanistik GmbH architecture firm, the GUI, the OBG, the Ergosign team and, of course, all those countless hard-working hands that made our plans reality.
We're already looking forward to the construction of the next building. 😉
Sources: Ergosign und FLOSUNDK architektur+urbanistik GmbH
Let's shape the future together! Meet us in our offices or virtually for an inspiring talk.


text:
Home »	News » Trends
US Streaming Growth Is Slowing, But That's Not A Bad Thing
Streaming growth is slowing down in the US according to the Nielsen Music Mid-Year Report. But don't hit the panic button, writes Bobby Owsinski, There's still plenty of room for growth worldwide.
By Bobby Owsinski of Music 3.0
The latest Nielsen Music Mid-Year Report shows that streaming has actually dropped by 5% in the U.S., which is causing some unneeded panic to occur in some sectors of the music business. With streaming growth predicted to continue for the next 10 years, any sign of a slowdown seems to contradict industry pundits, but this slowdown, and the report, might not be as bad as the headline makes it seem.
For one thing, the second half of the year is widely considered the busiest time of the year for music. As a result, it's likely that the the total streaming number will be higher by the end of the year. in fact, it's expected that the total number of streams in the U.S. and Canada will even surpass 1 trillion!
The fact of the matter is that the number of streams doesn't equate to the number of paying streaming subscribers. It's possible for average streaming rate per listener to drop while the number of subscribers still increases, which equates for more money in industry coffers.
Also, the Nielsen numbers only look at the U.S. and don't account for the rest of the world. Asia and South America are picking up subscribers at a greater pace than North America at this point, as the service (as well as paying for it) is somewhat new in those territories. Meanwhile, North America and Northern Europe are now somewhat mature markets where you'd naturally expect for a slowdown as market saturation approaches.
This may be good news for the streaming platforms of the world, but music markets now look towards home-grown artists more and more, as each territory's music scene develops. In fact, we're seeing more chart topping talent in North America than ever before (K-Pop, for instance).
So the slowdown in streaming shouldn't be seen as an alarm, but more as a gentle nudge that they heyday of big growth may be over, but the market will still continue to grow more slowly from here on out.
This story appears courtesy of HypeBot.
Music Industry HypeBot AAJ Staff


TermCoord's Android App – Search on IATE on the fly!
Great news for all of you, "terminology fanatics"! If you ever need to consult IATE on your phone, now there is a new tool that can help you! Check European terminology on the fly with the new application created by the Terminology Coordination Unit [DG TRAD] of the European Parliament searching in the EU terminology database IATE.
This small, lightweight application will allow every Android user to consult more than 8 million terms in 24 official EU languages, in a fast and user-friendly environment. Results come filtered by reliability and it is also possible to search in a specific subdomain.
This project is designed not only for translators, but for journalists and students as well. Thanks to its ease of use, everybody will be able to prompt a search in just few seconds.
The application has been developed by the communication trainees of the Terminology Coordination Unit and it's available on the Google Play Market, but a porting for other platforms is already planned as well.


text:
import os

class Project(object):
    def __init__(self):
        self.name = None
        self.path = None

    def open(self, name):
        path = os.path.join(os.getcwd(), 'projects', name)
        if not os.path.exists(path):
            os.makedirs(path)

        self.name = name
        self.path = path

    def get_path(self):
        if self.path and os.path.exists(self.path):
            return self.path
        else:
            return os.getcwd()

__project__ = Project()